Chemical compound
Pharmaceutical compound
5'-Guanidinonaltrindole Other names 5'-Guanidinonaltrindole, GNTI
5'-Guanidinyl-17-(cyclopropylmethyl)-6,7-dehydro-4,5α-epoxy-3,14-dihydroxy-6,7-2',3'-indolomorphinan
PubChem CID IUPHAR/BPS ChemSpider ChEMBL CompTox Dashboard (EPA ) Formula C 27 H 29 N 5 O 3 Molar mass 471.561 g·mol−1 3D model (JSmol )
c1cc2c(cc1NC(=N)N)c3c([nH]2)[C@H]4[C@@]56CCN([C@@H]([C@@]5(C3)O)Cc7c6c(c(cc7)O)O4)CC8CC8
InChI=1S/C27H29N5O3/c28-25(29)30-15-4-5-18-16(10-15)17-11-27(34)20-9-14-3-6-19(33)23-21(14)26(27,24(35-23)22(17)31-18)7-8-32(20)12-13-1-2-13/h3-6,10,13,20,24,31,33-34H,1-2,7-9,11-12H2,(H4,28,29,30)/t20-,24+,26+,27-/m1/s1
N Key:VLNHDKDBGWXJEE-GYHUNEDQSA-N
N
N Y (what is this?) (verify)
5'-Guanidinonaltrindole (5'-GNTI ) is an opioid antagonist used in scientific research which is highly selective for the κ opioid receptor . It is 5x more potent and 500 times more selective than the commonly used κ-opioid antagonist norbinaltorphimine .[ 1] It has a slow onset and long duration of action,[ 2] [ 3] and produces antidepressant effects in animal studies.[ 4] It also increases allodynia by interfering with the action of the κ-opioid peptide dynorphin .[ 5]
In addition to activity at the KOR, 5'-GNTI has been found to act as a positive allosteric modulator of the α1A -adrenergic receptor (EC50 = 41 nM), and this may contribute to its "severe transient effects".[ 6]
See also
References
^ Jones RM, Portoghese PS (May 2000). "5'-Guanidinonaltrindole, a highly selective and potent kappa-opioid receptor antagonist". European Journal of Pharmacology . 396 (1): 49–52. doi :10.1016/S0014-2999(00)00208-9 . PMID 10822054 .
^ Negus SS, Mello NK, Linsenmayer DC, Jones RM, Portoghese PS (October 2002). "Kappa opioid antagonist effects of the novel kappa antagonist 5'-guanidinonaltrindole (GNTI) in an assay of schedule-controlled behavior in rhesus monkeys". Psychopharmacology . 163 (3–4): 412–9. doi :10.1007/s00213-002-1038-x . PMID 12373442 . S2CID 6342513 .
^ Bruchas MR, Yang T, Schreiber S, Defino M, Kwan SC, Li S, Chavkin C (October 2007). "Long-acting kappa opioid antagonists disrupt receptor signaling and produce noncompetitive effects by activating c-Jun N-terminal kinase" . The Journal of Biological Chemistry . 282 (41): 29803–11. doi :10.1074/jbc.M705540200 . PMC 2096775 . PMID 17702750 .
^ Mague SD, Pliakas AM, Todtenkopf MS, Tomasiewicz HC, Zhang Y, Stevens WC, et al. (April 2003). "Antidepressant-like effects of kappa-opioid receptor antagonists in the forced swim test in rats". The Journal of Pharmacology and Experimental Therapeutics . 305 (1): 323–30. doi :10.1124/jpet.102.046433 . PMID 12649385 . S2CID 7235990 .
^ Obara I, Mika J, Schafer MK, Przewlocka B (October 2003). "Antagonists of the kappa-opioid receptor enhance allodynia in rats and mice after sciatic nerve ligation" . British Journal of Pharmacology . 140 (3): 538–46. doi :10.1038/sj.bjp.0705427 . PMC 1574046 . PMID 12970097 .
^ Munro TA, Huang XP, Inglese C, Perrone MG, Van't Veer A, Carroll FI, et al. (2013). "Selective κ opioid antagonists nor-BNI, GNTI and JDTic have low affinities for non-opioid receptors and transporters" . PLOS ONE . 8 (8): e70701. Bibcode :2013PLoSO...870701M . doi :10.1371/journal.pone.0070701 . PMC 3747596 . PMID 23976952 .
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